2. Academic Validation
  3. N6-Methyladenosine methyltransferase ZCCHC4 mediates ribosomal RNA methylation

N6-Methyladenosine methyltransferase ZCCHC4 mediates ribosomal RNA methylation

  • Nat Chem Biol. 2019 Jan;15(1):88-94. doi: 10.1038/s41589-018-0184-3.
Honghui Ma 1 2 3,  Xiaoyun Wang 4,  Jiabin Cai 5,  Qing Dai 2 3,  S Kundhavai Natchiar 6,  Ruitu Lv 1,  Kai Chen 2 3,  Zhike Lu 2 3,  Hao Chen 1,  Yujiang Geno Shi 1 7,  Fei Lan 1,  Jia Fan 5,  Bruno P Klaholz 6,  Tao Pan 8,  Yang Shi 9 10,  Chuan He 11 12 13
Affiliations

Affiliations

  • 1 Liver Cancer Institute, Zhongshan Hospital, Fudan University, and Institute of Biomedical Sciences, Fudan University, Shanghai, China.
  • 2 Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL, USA.
  • 3 Howard Hughes Medical Institute, The University of Chicago, Chicago, IL, USA.
  • 4 Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL, USA.
  • 5 Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, China.
  • 6 Centre for Integrative Biology (CBI), Department of Integrated Structural Biology, Institute of Genetics and of Molecular and Cellular Biology (IGBMC), CNRS, Inserm, Université de Strasbourg, Illkirch, France.
  • 7 Endocrinology Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • 8 Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL, USA. [email protected].
  • 9 Liver Cancer Institute, Zhongshan Hospital, Fudan University, and Institute of Biomedical Sciences, Fudan University, Shanghai, China. [email protected].
  • 10 Department of Cell Biology, Harvard Medical School, Boston, MA, USA. [email protected].
  • 11 Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL, USA. [email protected].
  • 12 Howard Hughes Medical Institute, The University of Chicago, Chicago, IL, USA. [email protected].
  • 13 Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL, USA. [email protected].
PMID: 30531910 DOI: 10.1038/s41589-018-0184-3
Abstract

N6-Methyladenosine (m6A) RNA modification is present in messenger RNAs (mRNA), ribosomal RNAs (rRNA), and spliceosomal RNAs (snRNA) in humans. Although mRNA m6A modifications have been extensively studied and shown to play critical roles in many cellular processes, the identity of m6A methyltransferases for rRNAs and the function of rRNA m6A modifications are unknown. Here we report a new m6A methyltransferase, ZCCHC4, which primarily methylates human 28S rRNA and also interacts with a subset of mRNAs. ZCCHC4 knockout eliminates m6A4220 modification in 28S rRNA, reduces global translation, and inhibits cell proliferation. We also find that ZCCHC4 protein is overexpressed in hepatocellular carcinoma tumors, and ZCCHC4 knockout significantly reduces tumor size in a xenograft mouse model. Our results highlight the functional significance of an rRNA m6A modification in translation and in tumor biology.

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